2. Academic Validation
  3. Generation and identification of a conditional knockout allele for the PSMD11 gene in mice

Generation and identification of a conditional knockout allele for the PSMD11 gene in mice

  • BMC Dev Biol. 2021 Feb 1;21(1):4. doi: 10.1186/s12861-020-00233-1.
Linlin Zhao 1,  Jinming Zhao 1,  Yingying Zhang 1,  Lele Wang 2,  Longyan Zuo 3,  Airu Niu 4,  Wei Zhang 5,  Xia Xue 6,  Suhong Zhao 5,  Chao Sun 1,  Kailin Li 1,  Jue Wang 1,  Zhimin Bian 7,  Xiaogang Zhao 8,  Dieter Saur 9,  Barbara Seidler 9,  Chuanxin Wang 2,  Tonggang Qi 10
Affiliations

Affiliations

  • 1 Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.
  • 2 Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.
  • 3 Department of Pathology, Liaocheng People's Hospital, Liaocheng, 252000, China.
  • 4 Department of Clinical Laboratory, Sanhe Yanjiao No.23 Hospital, Beijing, 065201, China.
  • 5 Department of Medical Imaging, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.
  • 6 Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.
  • 7 Comprehensive Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 8 Department of Thoracic Surgery/Key Laboratory of Thoracic Cancer in Universities of Shandong, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.
  • 9 The II. Medizinische Klinik und Poliklinik der Technischen Universität München, Ismaningerstr. 22, 81675, Munich, Germany.
  • 10 Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China. tg_qi@sdu.edu.cn.
PMID: 33517884 DOI: 10.1186/s12861-020-00233-1
Abstract

Background: Our previous study have shown that the PSMD11 protein was an important survival factor for Cancer cells except for its key role in regulation of assembly and activity of the 26S Proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11flx) in mice.

Results: It was found that homozygous PSMD11 flx/flx mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11flx/flx and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11-/-) were identified in E7.5-8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26CAG - CreERT2/+; PSMD11 flx/flx, and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive Apoptosis in MEFs.

Conclusions: In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 flx/flx mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.

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